it takes some serious talent to screw this up

I will never really understand why people bother to buy tetrakis(triphenylphosphine) palladium(0). On any given day, it's definitely the easiest reaction I do, and it always works. On a bad day, the bright yellow crystals are enough to make me feel a little better. (Also, palladium catalysis is MAGIC.) Apparently, it doesn't ship well and might show up in funny colors (unless maybe you get it from Strem). It only takes about half an hour.


Excimer asked me a long time ago to post the procedure I use to make this, and I'm finally getting around to it. One of my labmates googled this a while back, and it's never failed us. It also has the advantage of being free. Usually I work on about a hundredth of their scale, which still works well enough--I'll maybe never have an excuse to make over 100 grams of the stuff.

Store under nitrogen and in the dark--it's ready for whatever coupling reaction you want to throw it into. (This batch is going toward a Sonogashira and a Stille.)

easiest reaction ever!

I'll admit I don't have much to do with green chemistry. Sure, whatever, I'll use it if it'll do what I want done, but I'm not actively involved in green research. I've become a fan of it lately, though.

So this is the first ionic liquid I've ever had occasion to use. I also had to make it. (First time I've ever had to synthesize a solvent. Guess there's a first time for everything, eh?) Didn't mind, though, because the starting materials were already on the shelf. These guys over at Los Alamos & Oak Ridge made
1-Butyl-3-methylimidazolium bromide, which was pretty close to what I wanted. They used one of the reagents as solvent, which is a pretty cool idea and which also means you get to avoid the rotavap.[1] They claim the addition is exothermic, which I guess is a concern on a larger scale (which they had to deal with and I didn't). Add the iodobutane kinda slowly and then let it stir for a day or so.[2]

So it's stupid-easy to run, which makes me happy. They list a purification method that involves charcoal and a lyophilizer, but I didn't have one of those handy. For my purposes, though, trace impurities are not that much of a concern.[3] The NMR was the cleanest I've seen in a while.

Hopefully it will actually work in the reaction I'm going to throw it into.


[1] Don't know about you, but I hate waiting for solvent to evaporate. I'm not going to live forever, you know. I don't want to waste very much of that time watching a roundbottom spin, but invariably I do...
[2] For paranoia reasons, I had this one under nitrogen...another reference mentioned a problem with the iodide getting oxidized or something.
[3] The stuff they made was really super extra squeaky clean.

You're a Good Isomerizer, Charlie Brown

I've gushed about Paul Docherty's Totally Synthetic blog before, and the gushing is well-deserved: every week or so he summarizes the latest and greatest in total synthesis so I don't have to read those papers (and so I can read the ones pertinent to my own research). After reading his synopsis on Dave Evans' latest JACS on the synthesis of Salvinorin A, I fell in love with a particular step that Paul also lauded (if I may just steal the image from his post):


They took an internal alkyne with a stereocenter and isomerized it to the terminal alkyne in one step in good yield. This reaction, called the "acetylene zipper" by its creator, Charles Brown (the son of boron guru and Nobel Laureate H.C Brown), might be the simplest method of generating terminal alkynes, as internal alkynes are, by contrast, much easier to make by cross-coupling reactions.* The acetylene zipper, which, aside from having an awesome name, is a very simple, elegant reaction and it really works! (It's not terribly functional group-tolerant, but who needs those?)

The acetylene zipper works by generating a strong base that can "walk" the alkyne to the terminal position, where it's held in place by the formation of a terminal acetylide ion. Since acetylene protons are much more acidic than propargylic protons (pKa 25 vs 40ish), there is a large energetic barrier to deprotonate the propargylic proton once the acetylene is at the terminal position. Acetylenes have been reported zipping across alkyl chains anywhere from 1 to 30 carbons long. Any secondary carbons (bearing methyl groups or what have you) stop the zipper, and the acetylene isomerizes until it hits the terminal position. The best part of the reaction? It's done in seconds. Most substrates can be worked up in no time after adding the starting material. It literally takes more time to set up the reaction than it does for the reaction to complete!

The reaction requires a special superbase, potassium 3-aminopropylamide (KAPA). No other base works with this reaction (although the sodium analogue does work but in lower yield). There is something special about the "spacing" between the amine groups in KAPA that allows this isomerization to occur, as neither ethylenediamine nor putrescine work. There are several ways to generate it, the most common being 1,3-diaminopropane and KH. KH is a pain in the ass to deal with, so an alternative prep using lithium and KOt-Bu has been done which works nicely too.

Sorry, not materials-related, but still a very cool reaction. As Paul said, it "engenders incredible synthetic utility, and seems so simple," and I would have to agree.

** In my experience, anyway. Corey-Fuchs reactions never worked for me. Sonogashiras always do.

sonogashira party!

I'll start by admitting how much I love the Sonogashira coupling. It's a fun reaction, and it LOVES my substrates. Plus, it gives me an excuse to make Pd(Ph₃P)₄. Making tetrakis is one of those things you can do on a particularly bad lab day that is guaranteed to make you feel better. It's very hard to screw up, and you get shiny yellow crystals.[1] Anyway, I set three of these up the other day:

If you were wondering, yes, there appears to be a shortage of tiny little clamps in my lab. We just don't do much with 14/20 glassware (this is an exception of sorts). Maybe they're in the stockroom, but by the time I need one I'm always in the middle of setting something up, so I haven't checked. Yes, my oil bath is nasty looking. It was like that when I inherited it from the hood's previous occupant. The color reminds me of motor oil, which is a quick way to ick me out a little.[2]

Anyway, after my happy little reactions ran overnight, I had a nice little surprise waiting for me in one of the flasks:

It looked exactly like metallic copper, which it doesn't quite in the picture, but close enough. Does anyone know what it could be? I've seen palladium plate out of a reaction, but copper?[3] That just seems weird. It worked, though, so I'm not complaining.

I took all three of those through silica plugs, which was more time-consuming than I would have liked.[4] I know this is pretty routine, and barely worth reading about, but since some chemists seem to be complaining about the lack of pretty colors in their lives, I had to show mine off. (You have permission to be jealous now.) Here is one of the fractions I collected:

I know blue isn't too much to be excited about in the way of fluorescence (yeah, yeah, emission probability goes as ν³, I know, red is cooler) but it's still surprising to look at a TLC plate and be distracted by an unexpected glow from elsewhere on the bench.

[1] And then you wash them with ether. Mmm. Keeps getting better and better, doesn't it?

[2] Lest you think I'm just being girlie, I can and do change the oil in my car. But I have a texture problem with it. Ewwwwww, slimy!

[3] Pd-mirror is beautiful shiny stuff. (We at CBC like shiny things.) I wish I had a picture to show you, but I don't.

[4] Ever wonder how many YEARS of your life you've wasted staring at a rotavap?

what's in the flask:

Yesterday's mystery flask managed to confound pretty much everyone who guessed. Surprise, surprise: here's the reaction.

Here's a shot of the flask before the reaction with everything in there except the amine.

I know what you're thinking. "Dude, where's my solvent?" Everything is solid! ...At room temperature. The reaction is actually run at between 105 and 140 or so degrees, depending on the boiling point of the amine. Stick a septum on, blow nitrogen through it like crazy and inject the amine. This throws off water vapor, so pressure will build up. If you're not careful, you will hear a *POP* and rush over to see your septum off to the side. Folding it down and using a piece of wire to hold it in place seems to work well, but keep an eye on the bubbler. The lovely white crystals from yesterday's post can clog the needle.

The workup (which is simple but also a pain in the ass) and the rest of the procedure is detailled in this paper. As an added bonus, there's a bit about solar cells in there![1]

Beautiful reaction. It's never failed me. The only downside is that you should keep a LOT of chloroform handy, if you ever want your glassware to be clear instead of reddish in places.[2] Oh, and on this note, be sure to keep R long and greasy.



[1] Sadly, as is stated in the abstract, the solar cells they tried to make with these didn't quite work. Maybe sometime I'll have something to say about electrode interfaces. For the moment, though, I'd rather leave that one to the surface chemists and the engineers.

[2] Particularly if there are ground glass joints involved.

oxygen--part two

Back to something I started a while ago and didn't finish: how to generate singlet oxygen. Probably the best-known means is photosensitization--use a dye (Rose Bengal, Methylene Blue, etc.) and a lamp. The dye is photoexcited and transfers its energy to oxygen, giving the singlet.[1] While this can involve some pretty cool-looking lamps (see left), it doesn't have to--you can do it Dylan's way with a lamp from Home Depot. (This group has even managed to do it without solvent!) Photochemical reactions can have some scale-up issues, though, despite being super-cool.

Alternatively, you can use peroxide and things involving metals (ew, metals, ick). Molybdates, peroxotungstates and La(OH)₃ seem to work alright.[2] CaO₂ appears to be the most popular, but it sounds kinda tricky to make. (Anyone done this?)

And then there's a fun little reaction I did a while ago.[3] Uses a weird little hypervalent iodine compound--[Bis(trifluoroacetoxy)iodo]benzene, oft-abbreviated as "PIFA"--and catalytic H₂O₂ to generate singlet oxygen.

This was dead easy to set up and about the only thing I've done that's given a respectable yield. If a knuckle-dragging undergrad like me can manage not to screw this up, just about anyone can. As an added bonus, the benzofuran I started with was the color of yellow highlighter ink. (No picture, though. Sorry!)

[1] You really don't want to get me started on energy transfer, especially since I am already very excitable. Maybe a nice long post will appear about it in the future.

[2] Found a review on this a while back. Fairly short & sweet. Have fun.

[3] Here is the paper! Go try it! (Especially if it's a bad day and nothing else is working. This will make you feel better.)

Have you seen this girl?

A Japanese artist(?) has made a pretty creepy video of what he calls Ferrofluid sculptures. I have to say, this video creeps me out, but it does use ferrofluids, which are pretty awesome. A ferrofluid is a dispersion of iron nanoparticles in (usually) water, which can interact with magnetic fields to generate corrugated patterns that look like this:



Ferrofluids are more than just artsy and freaky-cool. Its magnetic properties have found use in the IT, optics and defense industries. They will probably be partly responsible for this guy looking for Sarah Connor.

And for the truly bored during this Festivus break, here's how to synthesize your very own ferrofluids. Have fun!

got science?

The ETH Zürich has a LOT of demonstration videos. Most of them are pretty awesome. These are for inorganic chemistry, though, and I prefer to think that d orbitals are imaginary because carbon doesn't have any. So don't take my word for it. Check it out. Pass it on!